The proposed research is aimed at providing additional information about the interactions between hemeproteins (hemoglobin and myoglobin) and water with which all proteins interacts in specific and non-specific ways. Thermodynamic information about the protein-water interactions will be obtained by measure changes in the functional properties of the protein when the activity of the solvent molecules is changed in a systematic fashion. Alteration in the protein-water interaction is accomplished by introducing high concentration of ionic and non-ionic solutes into the system. Selected solutes, which in general interact rather weakly with the protein will compete with the latter for water molecules in order to satisfy their own energetic criteria for solvation. The balance of hydration between protein and solute can be related to existing theories pertaining to protein hydration (e.g. Timasheff, S.N. Acc. Chem. Res. 3, 62 (1970)). By monitoring the binding of oxygen to the hemeprotein and at the same time measure oxygen solubility in the solvent, we can relate changes in the thermocynamic properties of the latter to differential interaction between solvent molecules and the protein. The juxtaposition of the hemoglobin tetramer, a finely tuned free energy transducer, and the monomeric non-allosteric myoglobin molecule, the extent to which differential hydration has been incorporated into the linked function of hemoglobin can be evaluated. The thermodynamic information that will be gathered in the course of the proposed research is a measure of the forces that sufficiently amplified render the protein insoluble. In other words, it may be possible to account for phase equilibria of proteins by changes in protein-water interactions. If this is the case, can abnormal solubility characteristics, such as the decreased solubility of sickle cell hemoglobin, be accounted for by irregular hydration patterns, maybe at the site of the mutation, that will favor aggregation. Since the overlap of hydration shells is the initial event in determining both protein solubility and protein-protein recognition, the acquisition of additional thermodynamic information pertaining to protein-water interactions is relevant.